A5053574087- Drug Transport and Resistance Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- Pharmacological Effects and Toxicity Studies
- Pharmacogenetics and Drug Metabolism
- Neonatal Health and Biochemistry
- Pediatric Hepatobiliary Diseases and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Trace Elements in Health
- Pregnancy and Medication Impact
- Glutathione Transferases and Polymorphisms
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Ion Transport and Channel Regulation
- Genomics, phytochemicals, and oxidative stress
- Folate and B Vitamins Research
- Alcohol Consumption and Health Effects
- Pancreatitis Pathology and Treatment
- Gastroesophageal reflux and treatments
- Ginger and Zingiberaceae research
- Hormonal Regulation and Hypertension
- Clinical Nutrition and Gastroenterology
- Hemoglobinopathies and Related Disorders
- Silymarin and Mushroom Poisoning
- Protein Kinase Regulation and GTPase Signaling
Consejo Nacional de Investigaciones Científicas y Técnicas
2013-2023
Institute of Physics Rosario
2017-2023
National University of Rosario
2009-2021
Instituto de Fisiología Vegetal
2000-2021
Instituto de Cardiología y Cirugía Cardiovascular
2012
University of Kentucky
2000-2008
University of Southern California
2008
Pontificia Universidad Católica de Chile
2008
The Graduate Center, CUNY
2000-2007
The expression of multidrug resistance-associated protein isoform 2 (mrp2), the ATP-dependent export pump that mediates transport glucuronic acid-, glutathione-, and sulfate-conjugated derivatives, was studied in rat small intestine. intestine divided into nine equal segments, mrp2 content analyzed homogenate brush border membrane preparations by Western analysis. present mainly proximal segments gradually decreased from jejunum to distal ileum. We also three different populations...
Estradiol-17beta-D-glucuronide (E(2)17G), an endogenous metabolite of estradiol, induces a potent dose-dependent and reversible inhibition bile flow in the rat. We analyzed effect single dose E(2)17G (15 micromol/kg, intravenously) to female rats on endocytic retrieval function canalicular multidrug resistance-associated protein 2 (Mrp2) pretreatment with dibutyryl-cyclic AMP (DBcAMP; 20 micromol/kg) these measures. Bile was maximally inhibited by 85% within 10 minutes returned 50% 100%...
Endocytic internalization of the multidrug resistance-associated protein 2 (Mrp2) was previously suggested to be involved in estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we evaluated rat whether a similar phenomenon occurs with bile salt export pump (Bsep) and ability DBcAMP prevent it. E217G (15 micromol/kg i.v.) impaired (BS) output induced Bsep internalization, as assessed by confocal microscopy Western blotting. Neither cholestasis nor occurred TR- rats lacking Mrp2....
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide. Sorafenib only drug available that improves overall survival of HCC patients. P-glycoprotein (P-gp), Multidrug resistance-associated proteins 2 and 3 (MRP2 3) Breast resistance protein (BCRP) are efflux pumps play a key role in chemoresistance. Their modulation by dietary compounds may affect intracellular accumulation therapeutic efficacy drugs substrates these transporters. Genistein (GNT) phytoestrogen abundant...
The effect of silymarin (SIL) on 17α–ethynylestradiol (EE)–induced cholestasis was evaluated in rats. EE (5 mg/kg, subcutaneously, daily, for 5 days) decreased both the bile–salt-dependent and bile–salt-independent fractions bile flow. decrease former associated to a reduction salt pool size (-58%), this completely prevented by SIL. This compound also counteracted inhibitory induced HCO 3 – but not glutathione output, 2 major determinants secretory rate maximum (Srm) tauroursodeoxycholate,...
Abstract The endogenous estradiol metabolite 17β-d-glucuronide (E217G) induces an acute cholestasis in rat liver coincident with retrieval of the canalicular transporters bile salt export pump (Bsep, Abcc11) and multidrug resistance-associated protein 2 (Mrp2, Abcc2) their associated loss function. We assessed participation Ca2+-dependent kinase C isoforms (cPKC) cholestatic manifestations E217G perfused (PRL) isolated hepatocyte couplets (IRHCs). In PRL, (2 μmol/liver; intraportal, single...
Estradiol 17β-D-glucuronide (E217G) is an endogenous, cholestatic metabolite that induces endocytic internalization of the canalicular transporters relevant to bile secretion: salt export pump (Bsep) and multidrug resistance–associated protein 2 (Mrp2). We assessed whether phosphoinositide 3-kinase (PI3K) involved in E217G-induced cholestasis. E217G activated PI3K according assessment phosphorylation final effector, kinase B (Akt). When inhibitor wortmannin (WM) was preadministered isolated...
We analyzed the expression of multidrug resistance-associated protein 2 (mrp2) in small intestine control female rats and during late pregnancy (19-20 days pregnancy) lactation (2-4, 10-14, 21 after delivery). Western blot analysis was performed on brush-border membranes prepared from different regions intestine. Expression mrp2 maximal proximal segments for all experimental groups, preserved pregnant rats, increased by 100% postpartum with respect to animals. Northern mRNA revealed a...
The molecular basis of perinatal changes occurring in major UDP-glucuronosyltransferase (UGT) family 1 isoforms and UGT2B1, a relevant isoform belonging to 2, was analyzed rat liver. Nonpregnant, pregnant (19-20 days pregnancy), two groups postpartum animals corresponding early middle stages lactation (2-4 10-12 after delivery, respectively) were studied. UGT activity determined UDP-N-acetylglucosamine-activated microsomes revealed that bilirubin, p-nitrophenol, ethynylestradiol (17beta-OH...
Estradiol-17beta-D-glucuronide (E2-17G) induces a marked but reversible inhibition of bile flow in the rat together with endocytic retrieval multidrug resistance-associated protein 2 (Mrp2) from canalicular membrane to intracellular structures. We analyzed effect pretreatment (100 min) microtubule inhibitor colchicine or lumicholchicine, its inactive isomer (1 micromol/kg iv), on changes and localization function Mrp2 induced by E2-17G (15 iv). Bile biliary excretion bilirubin, an endogenous...
Despite its toxicity, acetaminophen (APAP) is used increasingly as an analgesic, antipyretic, and anti-inflammatory agent. We examined the effect of prior exposure to APAP on biliary urinary elimination. The elimination a test dose (150 mg/kg i.v.) was determined in male Wistar rats 24 h after pretreatment with vehicle, single (1.0 g/kg i.p.), or increasing daily doses (0.2, 0.3, 0.6, 1.0 g/kg/day i.p.) APAP. Although parent minimally affected, excretion glucuronide significantly decreased...
Background Benznidazole (BZL) is the only antichagasic drug available in most endemic countries. Its effect on expression and activity of drug-metabolizing transporter proteins has not been studied yet. Methodology/Principal Findings Expression P-glycoprotein (P-gp), Multidrug resistance-associated protein 2 (MRP2), Cytochrome P450 3A4 (CYP3A4), Glutathione S-transferase (GST) were evaluated HepG2 cells after treatment with BZL. was estimated by immunoblotting real time PCR. P-gp MRP2...